In the developed world, improved hygiene and reduced exposure to pathogens have led to a decrease in the infectious burden that is hypothesised to be associated with the rise of allergies and autoimmune diseases. Helminths have evolved to become experts at subverting immune surveillance. Their ability to effectively “cloak” themselves through potent and persistent immune tempering of the host immune response has piqued scientific interest in their potential as an alternate therapy for human inflammatory diseases. While severe helminth infection is known to cause immunopathological complications within its human host, recent evidence has suggested a more harmonious host-parasite interplay. Several recent studies have revealed that helminth secretions may protect their human host from a number of autoimmune diseases including inflammatory bowel disease, multiple sclerosis and type 1 diabetes. This study reports on the synthesis of hookworm-derived peptides for the development of a potential therapeutic treatment for autoimmune disease. Several ShK-like peptides from the Ancylostoma caninum and Necator americanus hookworm secretions were produced using solid phase peptide synthesis. Cytometric bead array, intracellular cytokine staining and functional T-cell assessment assays were used to investigate the biological effects of the peptides on human peripheral blood mononuclear cells (PBMC). It was shown that two peptides, A1 and N1 significantly decreased the production of inflammatory cytokines on human PBMCs and the proliferation of CD3/CD28 activated T cells. Studies using nuclear magnetic resonance spectroscopy of the active peptides A1 and N1 revealed similarities to the three dimensional structure of the ShK toxin. The A1 and N1 peptides also attenuated the symptoms of colitis in the TNBS-induced mouse model. These results suggest that both peptides may be potential drug leads for the treatment of autoimmune diseases.